Therapeutic management options for stage III non-small cell lung cancer

Table 3 Prospective trials for hyperfractionated radiation schedules for non-small-cell lung cancer treatment

Ref.	Phase	Study design	Chemo regimen	RT	No. of patients	Stage	Median f/u (mo)	OS	Median OS (mo)	Response rate	Toxicity
RTOG 83-11 Cox et al[106] (1990)	1 and 2	Randomized 1 of 5 dose groups: 60, 64.8, 69.6, 74.4, 79.2 Gy	None	Dose delivered in 1.2 Gy twice daily fxns	848	III	N/A	2-yr, 29% (69.6 Gy arm)	13 (69.6 Gy arm)		Risk for severe/ life-threatening pneumonitis- 2.6% (60 Gy), 5.7% (64.8 Gy), 5.7% (69.6 Gy), 8.1% (74.4 Gy)
RTOG 8808/ ECOG 4588 Sause et al[107] (2000)	3	Conv. RT + chemo vs hyperFRT vs conv. RT	Cisplatin/ vinblastin	Conv RT: 60 Gy in 2 Gy daily fxns HyperFRT: 69.6 Gy in 1.2 Gy twice daily fxns	458	II-IIIB, unresectable	> 60	5-yr, 8%, 6%, 5%	13.2, 12, 11.4		6 G4+ RT-related toxic events-4 of them in hyperFRT arm
RTOG 9410 Curran et al[51] (2010)	3	Sequential chemoRT (conv., arm 1) vs concurrent chemoRT (conv., arm 2) vs concurrent chemoRT (hyperFRT, arm 3)	Cisplatin/vinblastine (arms 1 and 2) Cisplatin/etoposide (arm 3)	Conv: 63 Gy in 1.8 daily fxns HyperFRT: 69.6 Gy in 1.2 Gy twice daily fxns	610	II-III, inoperable	132	5-yr, 10%, 16%, 13%)	14.6, 17, 15.6	ORR- 61%, 70%, 65%	G3+ acute esophagitis- 4%, 22%, 45% No difference in G5 toxicities
Saunders et al[112] (1999)		CHART vs conv. RT	None	Conv RT: 60 Gy in 2 Gy daily fxns HyperFRT: 54 Gy in 1.5, 3 x daily fxns, for consecutive days	563	III	> 48	2-yr, 29% vs 20% (P = 0.004) 2-yr, 33% vs 19% if SCC			Severe dysphagia, 19% vs 3%
ARO 97-1 Baumann et al[113] (2011)		CHARTWEL vs conv. RT	None	Conv RT: 66 Gy in 2 Gy fxns for 6.5 wk CHARTWEL: 60 Gy in 1.5, 3 x daily fxns for 2.5 wk	460	I-IIIB	40.8	2-yr, 31% vs 32% 3-yr, 22% vs 18% 5-yr, 11% vs 7%			Higher incidence of acute dysphagia with CHARTWEL
INCH trial Hatton et al[114] (2011)		Induction chemo + CHART vs CHART alone	Cisplatin/vinorelbine	54 Gy in 1.5 Gy fxns (3 x daily) for 12 consecutive days	46	I-III, inoperable	33		25 vs 17		G3/4 adverse effects 65% vs 57%
ECOG 2597 Belani et al[115] (2005)	3	Induction chemo + conv. RT vs induction chemo + CHART	Carboplatin/paclitaxel	Conventional RT: 64 Gy in2 Gy fxns (daily) 57.6 Gy in 1.6 Gy fxns (3 x daily) for 15 d	141	IIIA/B, inoperable	> 36	2-yr, 24% vs 44% 3-yr, 14% vs 34%	14.9 vs 20.3	ORR, 22% vs 25%	Acute esophagitis 16% vs 25% G3/4 acute pulmonary toxicity observed in conventional RT arm
Hatton et al[100] (2016)	1	Randomized 1 of 4 dose groups: 54, 57.6, 61.2, 64.8 Gy	None	Each dose group delivered in 1.8 Gy, 2-6 fxns daily	18	IIIA/B	21	2-yr, 49% (entire cohort)	24 (entire cohort)	ORR, 61% (entire cohort) CR, 28% (entire cohort)	G3/4 adverse effects in 6 of 18 patients No dose-limiting toxicities

SCC: Squamous cell carcinoma; OS: Overall survival; RT: Radiotherapy.